Devices, systems, and methods for assessing a vessel

ABSTRACT

An intravascular system includes at least one pressure-sensing instrument sized and shaped for introduction into a vessel of a patient; a processing unit in communication with the pressure-sensing instrument, the processing unit configured to: obtain proximal pressure measurements for at least one cardiac cycle of the patient while the pressure-sensing instrument is positioned proximal of a stenosis of the vessel; obtain distal pressure measurements while the pressure-sensing instrument is positioned distal of the stenosis; select a diagnostic window within a cardiac cycle by identifying a change in sign of a slope associated with the proximal and/or distal pressure measurements, wherein the diagnostic window encompasses only a portion of the cardiac cycle of the patient; calculate a pressure ratio between the distal and proximal obtained during the diagnostic window; and output the calculated pressure ratio to a display device in communication with the processing unit.

CROSS-REFERENCE TO PRIOR APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/094,155, filed on Nov. 10, 2020, now U.S. Pat. No. 11,672,433, whichis a continuation of U.S. patent application Ser. No. 15/745,651, filedon Jan. 17, 2018, now U.S. Pat. No. 10,849,512, which is the U.S.National Phase application under 35 U.S.C. § 371 of InternationalApplication No. PCT/EP2016/066917, filed on Jul. 15, 2016, which claimsthe benefit of U.S. Provisional Patent Application No. 62/194,066, filedon Jul. 17, 2015. These applications are hereby incorporated byreference herein.

TECHNICAL FIELD

The present disclosure relates generally to the assessment of vesselsand, in particular, the assessment of the severity of a blockage orother restriction to the flow of fluid through a vessel. Aspects of thepresent disclosure are particularly suited for evaluation of biologicalvessels in some instances. For example, some particular embodiments ofthe present disclosure are specifically configured for the evaluation ofa stenosis of a human blood vessel.

BACKGROUND

A currently accepted technique for assessing the severity of a stenosisin a blood vessel, including ischemia causing lesions, is fractionalflow reserve (FFR). FFR is a calculation of the ratio of a distalpressure measurement (taken on the distal side of the stenosis) relativeto a proximal pressure measurement (taken on the proximal side of thestenosis). FFR provides an index of stenosis severity that allowsdetermination as to whether the blockage limits blood flow within thevessel to an extent that treatment is required. The normal value of FFRin a healthy vessel is 1.00, while values less than about 0.80 aregenerally deemed significant and require treatment. Common treatmentoptions include angioplasty and stenting.

Coronary blood flow is unique in that it is affected not only byfluctuations in the pressure arising proximally (as in the aorta) but isalso simultaneously affected by fluctuations arising distally in themicrocirculation. Accordingly, it is not possible to accurately assessthe severity of a coronary stenosis by simply measuring the fall in meanor peak pressure across the stenosis because the distal coronarypressure is not purely a residual of the pressure transmitted from theaortic end of the vessel. As a result, for an effective calculation ofFFR within the coronary arteries, it is necessary to reduce the vascularresistance within the vessel. Currently, pharmacological hyperemicagents, such as adenosine, are administered to reduce and stabilize theresistance within the coronary arteries. These potent vasodilator agentsreduce the dramatic fluctuation in resistance (predominantly by reducingthe microcirculation resistance associated with the systolic portion ofthe heart cycle) to obtain a relatively stable and minimal resistancevalue.

However, the administration of hyperemic agents is not always possibleor advisable. First, the clinical effort of administering hyperemicagents can be significant. In some countries (particularly the UnitedStates), hyperemic agents such as adenosine are expensive, and timeconsuming to obtain when delivered intravenously (IV). In that regard,IV-delivered adenosine is generally mixed on a case-by-case basis in thehospital pharmacy. It can take a significant amount of time and effortto get the adenosine prepared and delivered to the operating area. Theselogistic hurdles can impact a physician's decision to use FFR. Second,some patients have contraindications to the use of hyperemic agents suchas asthma, severe COPD, hypotension, bradycardia, low cardiac ejectionfraction, recent myocardial infarction, and/or other factors thatprevent the administration of hyperemic agents. Third, many patientsfind the administration of hyperemic agents to be uncomfortable, whichis only compounded by the fact that the hyperemic agent may need to beapplied multiple times during the course of a procedure to obtain FFRmeasurements. Fourth, the administration of a hyperemic agent may alsorequire central venous access (e.g., a central venous sheath) that mightotherwise be avoided. Finally, not all patients respond as expected tohyperemic agents and, in some instances, it is difficult to identifythese patients before administration of the hyperemic agent.

Accordingly, there remains a need for improved devices, systems, andmethods for assessing the severity of a blockage in a vessel and, inparticular, a stenosis in a blood vessel. In that regard, there remainsa need for improved devices, systems, and methods for assessing theseverity of a stenosis in the coronary arteries that do not require theadministration of hyperemic agents.

SUMMARY

Embodiments of the present disclosure are configured to assess theseverity of a blockage in a vessel and, in particular, a stenosis in ablood vessel. In some particular embodiments, the devices, systems, andmethods of the present disclosure are configured to assess the severityof a stenosis in the coronary arteries without the administration of ahyperemic agent. A subset of intravascular pressure measurementsobtained during a diagnostic window can be used to calculate a pressureratio. The diagnostic window can be determined without utilizingelectrocardiogram (ECG) data, in some instances. Rather, in suchinstances, the intravascular pressure measurements can be divided intodifferent time periods, and slopes respectively associated with eachtime period can be used to identify one or more features of theintravascular pressure measurements, a cardiac cycle of the patient,and/or the diagnostic window.

In some instances, an intravascular system is provided. The systemincludes at least one pressure-sensing instrument sized and shaped forintroduction into a vessel of a patient; a processing unit incommunication with the at least one pressure-sensing instrument, theprocessing unit configured to: obtain proximal pressure measurements forat least one cardiac cycle of the patient from the at least onepressure-sensing instrument while the at least one pressure-sensinginstrument is positioned within the vessel at a position proximal of astenosis of the vessel; obtain distal pressure measurements for the atleast one cardiac cycle of the patient from the at least onepressure-sensing instrument while the at least one pressure-sensinginstrument is positioned within the vessel at a position distal of thestenosis of the vessel; select a diagnostic window within a cardiaccycle of the patient by identifying a change in sign of a slopeassociated with at least one of the proximal pressure measurements orthe distal pressure measurements, wherein the diagnostic windowencompasses only a portion of the cardiac cycle of the patient;calculate a pressure ratio between the distal pressure measurementsobtained during the diagnostic window and the proximal pressuremeasurements obtained during the diagnostic window; and output thecalculated pressure ratio to a display device in communication with theprocessing unit.

In some embodiments, the processing unit is configured to select adiagnostic window without using electrocardiogram (ECG) data. In someembodiments, the proximal and distal pressure measurements are obtainedwithout administration of a hyperemic agent. In some embodiments, theprocessing circuit is further configured to calculate the slope overmultiple time periods within the cardiac cycle. In some embodiments, asingle time period encompasses only a portion of the cardiac cycle. Insome embodiments, time periods within the cardiac cycle have the sameduration. In some embodiments, the processing circuit is furtherconfigured to calculate the slope over multiple time periods of afurther cardiac cycle, wherein the time periods of the further cardiaccycle have a different duration than the time periods of the cardiaccycle. In some embodiments, a duration of the time periods is based on aduration of a cardiac cycle. In some embodiments, a duration of the timeperiods is based on a duration of time periods in one or more previouscardiac cycles. In some embodiments, consecutive time periods at leastpartially overlap in time. In some embodiments, a starting point ofconsecutive time periods are offset based on an acquisition rate of theat least one pressure-sensing instrument.

In some embodiments, the processing unit is further configured toidentify a sign change of the slope based on calculation of the slopeover the plurality of time periods. In some embodiments, the processingunit is further configured to determine, based on the sign change of theslope, at least one of: a minimum pressure measurement, a peak pressuremeasurement, a beginning of the cardiac cycle, an ending of the cardiaccycle, a beginning of systole, an ending of diastole, a starting pointof the diagnostic window, or an ending point of the diagnostic window.In some embodiments, the processing unit is further configured todetermine a starting point of the diagnostic window based on the signchange of the slope. In some embodiments, the starting point of thediagnostic window is offset from the sign change of the slope. In someembodiments, the processing unit is further configured to determine apeak pressure measurement based on the sign change of the slope. In someembodiments, the peak pressure measurement is offset from the signchange of the slope. In some embodiments, the processing unit is furtherconfigured to determine a starting point of the diagnostic window basedon the peak pressure measurement. In some embodiments, the startingpoint of the diagnostic window is offset from the peak pressuremeasurement. In some embodiments, the processing unit is furtherconfigured to determine a maximum negative slope occurring after thepeak pressure measurement. In some embodiments, the processing unit isfurther configured to determine a starting point of the diagnosticwindow based on the maximum negative slope. In some embodiments, thestarting point of the diagnostic window is offset from the maximumnegative slope. In some embodiments, the processing unit is furtherconfigured to determine a further sign change of the slope. In someembodiments, the processing unit is further configured to determine aminimum pressure measurement based on the further sign change of theslope. In some embodiments, the minimum pressure measurement is offsetfrom the further sign change of the slope. In some embodiments, theprocessing unit is further configured to determine an ending point ofthe diagnostic window based on the minimum pressure measurement. In someembodiments, the ending point of the diagnostic window is offset fromthe minimum pressure measurement.

In some embodiments, the at least one pressure-sensing instrumentcomprises: a first pressure-sensing instrument sized and shaped toobtain the proximal pressure measurements while positioned within thevessel at a position proximal of the stenosis of the vessel; and asecond pressure-sensing instrument sized and shaped to obtain the distalpressure measurements while positioned within the vessel at a positiondistal of the stenosis of the vessel. In some embodiments, at least oneof the first or second pressure-sensing instruments comprises acatheter, a guide wire, or a guide catheter. In some embodiments, thefirst pressure-sensing instrument is a catheter and the secondpressure-sensing instrument is a guide wire.

In some instances, a method of evaluating a vessel of a patient isprovided. The method includes receiving, at a processing unit incommunication with at least one pressure-sensing instrument sized andshaped for introduction into a vessel of the patient, proximal pressuremeasurements for at least one cardiac cycle of the patient while the atleast one pressure-sensing instrument is positioned within the vessel ata position proximal of a stenosis of the vessel; receiving, at theprocessing unit, distal pressure measurements for the at least onecardiac cycle of the patient while the at least one pressure-sensinginstrument is positioned within the vessel at a position distal of thestenosis of the vessel; selecting, using the processing unit, adiagnostic window within a cardiac cycle of the patient by identifying achange in sign of a slope associated with at least one of the proximalpressure measurements or the distal pressure measurements, wherein thediagnostic window encompasses only a portion of the cardiac cycle of thepatient; calculating, using the processing unit, a pressure ratiobetween the distal pressure measurements obtained during the diagnosticwindow and the proximal pressure measurements obtained during thediagnostic window; and outputting, using the processing unit, thecalculated pressure ratio to a display device in communication with theprocessing unit.

In some embodiments, the selecting a diagnostic window does not includeusing electrocardiogram (ECG) data. In some embodiments, the obtainingproximal pressure measurements and the obtaining distal pressuremeasurements do not include administering a hyperemic agent. In someembodiments, the method further includes calculating, using theprocessing circuit, the slope over multiple time periods within thecardiac cycle. In some embodiments, a single time period encompassesonly a portion of the cardiac cycle. In some embodiments, time periodswithin the cardiac cycle have the same duration. In some embodiments,the method further includes calculating the slope over multiple timeperiods of a further cardiac cycle, wherein the time periods of thefurther cardiac cycle have a different duration than the time periods ofthe cardiac cycle. In some embodiments, a duration of the time periodsis based on a duration of a cardiac cycle. In some embodiments, aduration of the time periods is based on a duration of time periods inone or more previous cardiac cycles. In some embodiments, consecutivetime periods at least partially overlap in time. In some embodiments, astarting point of consecutive time periods are offset based on anacquisition rate of the at least one pressure-sensing instrument.

In some embodiments, the method further includes identifying, using theprocessing unit, a sign change of the slope based on the slopecalculated over the plurality of time periods. In some embodiments, themethod further includes determining, using the processing unit and basedon the sign change of the slope, at least one of: a minimum pressuremeasurement, a peak pressure measurement, a beginning of the cardiaccycle, an ending of the cardiac cycle, a beginning of systole, an endingof diastole, a starting point of the diagnostic window, or an endingpoint of the diagnostic window. In some embodiments, the method furtherincludes determining, using the processing unit, a starting point of thediagnostic window based on the sign change of the slope. In someembodiments, the starting point of the diagnostic window is offset fromthe sign change of the slope. In some embodiments, the method furtherincludes determining, using the processing unit, a peak pressuremeasurement based on the sign change of the slope. In some embodiments,the peak pressure measurement is offset from the sign change of theslope. In some embodiments, the method further includes determining,using the processing unit, a starting point of the diagnostic windowbased on the peak pressure measurement. In some embodiments, thestarting point of the diagnostic window is offset from the peak pressuremeasurement. In some embodiments, the method further includesdetermining, using the processing unit, a maximum negative slopeoccurring after the peak pressure measurement. In some embodiments, themethod further includes determining, using the processing unit, astarting point of the diagnostic window based on the maximum negativeslope. In some embodiments, the starting point of the diagnostic windowis offset from the maximum negative slope. In some embodiments, themethod further includes determining, using the processing unit, afurther sign change of the slope. In some embodiments, the methodfurther includes determining, using the processing unit, a minimumpressure measurement based on the further sign change of the slope. Insome embodiments, the minimum pressure measurement is offset from thefurther sign change of the slope. In some embodiments, the methodfurther includes determining, using the processing unit, an ending pointof the diagnostic window based on the minimum pressure measurement. Insome embodiments, the ending point of the diagnostic window is offsetfrom the minimum pressure measurement.

In some embodiments, the method further includes introducing a firstpressure-sensing instrument into the vessel of the patient proximal ofthe stenosis of the vessel; and introducing a second pressure-sensinginstrument into the vessel of the patient distal of the stenosis of thevessel. In some embodiments, the receiving proximal pressuremeasurements includes receiving proximal pressure measurements while thefirst pressure-sensing instrument is positioned within the vessel at aposition proximal of the stenosis of the vessel; and the receivingdistal pressure measurements includes receiving distal pressuremeasurements while the second pressure-sensing instrument is positionedwithin the vessel at a position distal of the stenosis of the vessel. Insome embodiments, the method further includes identifying a treatmentoption based on the calculated pressure ratio; and performing theidentified treatment option.

Additional aspects, features, and advantages of the present disclosurewill become apparent from the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

Illustrative embodiments of the present disclosure will be describedwith reference to the accompanying drawings, of which:

FIG. 1 is a diagrammatic perspective view of a vessel having a stenosisaccording to an embodiment of the present disclosure.

FIG. 2 is a diagrammatic, partial cross-sectional perspective view of aportion of the vessel of FIG. 1 taken along section line 2-2 of FIG. 1 .

FIG. 3 is a diagrammatic, partial cross-sectional perspective view ofthe vessel of FIGS. 1 and 2 with instruments positioned thereinaccording to an embodiment of the present disclosure.

FIG. 4 is a diagrammatic, schematic view of a system according to anembodiment of the present disclosure.

FIG. 5 is a graphical representation of measured pressure and velocitywithin a vessel, annotated to identify a diagnostic window, according toan embodiment of the present disclosure.

FIG. 6 is a graphical representation of identifying a feature of apressure waveform, cardiac cycle, and/or a diagnostic window using anECG signal.

FIG. 7 is a graphical representation of a diagnostic window identifiedbased on the feature of FIG. 6 .

FIG. 8 is a graphical representation of a diagnostic window identifiedbased on the feature of FIG. 6 according to another embodiment of thepresent disclosure

FIG. 9 is a graphical representation of a segment of a pressurewaveform.

FIG. 10 is a pair of graphical representations, where the top graphicalrepresentation illustrates a segment-by-segment analysis of the pressurewaveform and the bottom graphical representation illustrates a slope ofthe pressure waveform associated with each segment.

FIG. 11 is a pair of graphical representations similar to that of FIG.10 , but where the segment slope waveform of the bottom graphicalrepresentation has been shifted relative the segment slope waveform ofFIG. 10 .

FIG. 12 is a graphical representation of identifying a feature of apressure waveform, a cardiac cycle, and/or a diagnostic window, usingthe segment slope waveform.

FIG. 13 is a graphical representation of identifying a diagnostic windowbased on the feature of FIG. 12 .

FIG. 14 is a flow diagram of a method of evaluating a vessel of apatient.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It is nevertheless understood that no limitation tothe scope of the disclosure is intended. Any alterations and furthermodifications to the described devices, systems, and methods, and anyfurther application of the principles of the present disclosure arefully contemplated and included within the present disclosure as wouldnormally occur to one skilled in the art to which the disclosurerelates. In particular, it is fully contemplated that the features,components, and/or steps described with respect to one embodiment may becombined with the features, components, and/or steps described withrespect to other embodiments of the present disclosure. For the sake ofbrevity, however, the numerous iterations of these combinations will notbe described separately.

Referring to FIGS. 1 and 2 , shown therein is a vessel 100 having astenosis according to an embodiment of the present disclosure. In thatregard, FIG. 1 is a diagrammatic perspective view of the vessel 100,while FIG. 2 is a partial cross-sectional perspective view of a portionof the vessel 100 taken along section line 2-2 of FIG. 1 . Referringmore specifically to FIG. 1 , the vessel 100 includes a proximal portion102 and a distal portion 104. A lumen 106 extends along the length ofthe vessel 100 between the proximal portion 102 and the distal portion104. In that regard, the lumen 106 is configured to allow the flow offluid through the vessel. In some instances, the vessel 100 is asystemic blood vessel. In some particular instances, the vessel 100 is acoronary artery. In such instances, the lumen 106 is configured tofacilitate the flow of blood through the vessel 100.

As shown, the vessel 100 includes a stenosis 108 between the proximalportion 102 and the distal portion 104. Stenosis 108 is generallyrepresentative of any blockage or other structural arrangement thatresults in a restriction to the flow of fluid through the lumen 106 ofthe vessel 100. Embodiments of the present disclosure are suitable foruse in a wide variety of vascular applications, including withoutlimitation coronary, peripheral (including but not limited to lowerlimb, carotid, and neurovascular), renal, and/or venous. Where thevessel 100 is a blood vessel, the stenosis 108 may be a result of plaquebuildup, including without limitation plaque components such as fibrous,fibro-lipidic (fibro fatty), necrotic core, calcified (dense calcium),blood, fresh thrombus, and mature thrombus. Generally, the compositionof the stenosis will depend on the type of vessel being evaluated. Inthat regard, it is understood that the concepts of the presentdisclosure are applicable to virtually any type of blockage or othernarrowing of a vessel that results in decreased fluid flow.

Referring more particularly to FIG. 2 , the lumen 106 of the vessel 100has a diameter 110 proximal of the stenosis 108 and a diameter 112distal of the stenosis. In some instances, the diameters 110 and 112 aresubstantially equal to one another. In that regard, the diameters 110and 112 are intended to represent healthy portions, or at leasthealthier portions, of the lumen 106 in comparison to stenosis 108.Accordingly, these healthier portions of the lumen 106 are illustratedas having a substantially constant cylindrical profile and, as a result,the height or width of the lumen has been referred to as a diameter.However, it is understood that in many instances these portions of thelumen 106 will also have plaque buildup, a non-symmetric profile, and/orother irregularities, but to a lesser extent than stenosis 108 and,therefore, will not have a cylindrical profile. In such instances, thediameters 110 and 112 are understood to be representative of a relativesize or cross-sectional area of the lumen and do not imply a circularcross-sectional profile.

As shown in FIG. 2 , stenosis 108 includes plaque buildup 114 thatnarrows the lumen 106 of the vessel 100. In some instances, the plaquebuildup 114 does not have a uniform or symmetrical profile, makingangiographic evaluation of such a stenosis unreliable. In theillustrated embodiment, the plaque buildup 114 includes an upper portion116 and an opposing lower portion 118. In that regard, the lower portion118 has an increased thickness relative to the upper portion 116 thatresults in a non-symmetrical and non-uniform profile relative to theportions of the lumen proximal and distal of the stenosis 108. As shown,the plaque buildup 114 decreases the available space for fluid to flowthrough the lumen 106. In particular, the cross-sectional area of thelumen 106 is decreased by the plaque buildup 114. At the narrowest pointbetween the upper and lower portions 116, 118 the lumen 106 has a height120, which is representative of a reduced size or cross-sectional arearelative to the diameters 110 and 112 proximal and distal of thestenosis 108. Note that the stenosis 108, including plaque buildup 114is exemplary in nature and should be considered limiting in any way. Inthat regard, it is understood that the stenosis 108 has other shapesand/or compositions that limit the flow of fluid through the lumen 106in other instances. While the vessel 100 is illustrated in FIGS. 1 and 2as having a single stenosis 108 and the description of the embodimentsbelow is primarily made in the context of a single stenosis, it isnevertheless understood that the devices, systems, and methods describedherein have similar application for a vessel having multiple stenosisregions.

Referring now to FIG. 3 , the vessel 100 is shown with instruments 130and 132 positioned therein according to an embodiment of the presentdisclosure. In general, instruments 130 and 132 may be any form ofdevice, instrument, or probe sized and shaped to be positioned within avessel. In the illustrated embodiment, instrument 130 is generallyrepresentative of a guide wire, while instrument 132 is generallyrepresentative of a catheter. In that regard, instrument 130 extendsthrough a central lumen of instrument 132. However, in otherembodiments, the instruments 130 and 132 take other forms. In thatregard, the instruments 130 and 132 are of similar form in someembodiments. For example, in some instances, both instruments 130 and132 are guide wires. In other instances, both instruments 130 and 132are catheters. On the other hand, the instruments 130 and 132 are ofdifferent form in some embodiments, such as the illustrated embodiment,where one of the instruments is a catheter and the other is a guidewire. Further, in some instances, the instruments 130 and 132 aredisposed coaxial with one another, as shown in the illustratedembodiment of FIG. 3 . In other instances, one of the instrumentsextends through an off-center lumen of the other instrument. In yetother instances, the instruments 130 and 132 extend side-by-side. Insome particular embodiments, at least one of the instruments is as arapid-exchange device, such as a rapid-exchange catheter. In suchembodiments, the other instrument is a buddy wire or other deviceconfigured to facilitate the introduction and removal of therapid-exchange device. Further still, in other instances, instead of twoseparate instruments 130 and 132 a single instrument is utilized. Inthat regard, the single instrument incorporates aspects of thefunctionalities (e.g., data acquisition) of both instruments 130 and 132in some embodiments.

Instrument 130 is configured to obtain diagnostic information about thevessel 100. In that regard, the instrument 130 includes one or moresensors, transducers, and/or other monitoring elements configured toobtain the diagnostic information about the vessel. The diagnosticinformation includes one or more of pressure, flow (velocity), images(including images obtained using ultrasound (e.g., IVUS), OCT, thermal,and/or other imaging techniques), temperature, and/or combinationsthereof. The one or more sensors, transducers, and/or other monitoringelements are positioned adjacent a distal portion of the instrument 130in some instances. In that regard, the one or more sensors, transducers,and/or other monitoring elements are positioned less than 30 cm, lessthan 10 cm, less than 5 cm, less than 3 cm, less than 2 cm, and/or lessthan 1 cm from a distal tip 134 of the instrument 130 in some instances.In some instances, at least one of the one or more sensors, transducers,and/or other monitoring elements is positioned at the distal tip of theinstrument 130.

The instrument 130 includes at least one element configured to monitorpressure within the vessel 100. The pressure monitoring element can takethe form a piezo-resistive pressure sensor, a piezo-electric pressuresensor, a capacitive pressure sensor, an electromagnetic pressuresensor, a fluid column (the fluid column being in communication with afluid column sensor that is separate from the instrument and/orpositioned at a portion of the instrument proximal of the fluid column),an optical pressure sensor, and/or combinations thereof. In someinstances, one or more features of the pressure monitoring element areimplemented as a solid-state component manufactured using semiconductorand/or other suitable manufacturing techniques. Examples of commerciallyavailable guide wire products that include suitable pressure monitoringelements include, without limitation, the PrimeWire PRESTIGE® pressureguide wire, the PrimeWire® pressure guide wire, and the ComboWire® XTpressure and flow guide wire, each available from Volcano Corporation,as well as the PressureWire™ Certus guide wire and the PressureWire™Aeris guide wire, each available from St. Jude Medical, Inc. Generally,the instrument 130 is sized such that it can be positioned through thestenosis 108 without significantly impacting fluid flow across thestenosis, which would impact the distal pressure reading. Accordingly,in some instances the instrument 130 has an outer diameter of 0.018″ orless. In some embodiments, the instrument 130 has an outer diameter of0.014″ or less.

Instrument 132 is also configured to obtain diagnostic information aboutthe vessel 100. In some instances, instrument 132 is configured toobtain the same diagnostic information as instrument 130. In otherinstances, instrument 132 is configured to obtain different diagnosticinformation than instrument 130, which may include additional diagnosticinformation, less diagnostic information, and/or alternative diagnosticinformation. The diagnostic information obtained by instrument 132includes one or more of pressure, flow (velocity), images (includingimages obtained using ultrasound (e.g., IVUS), OCT, thermal, and/orother imaging techniques), temperature, and/or combinations thereof.Instrument 132 includes one or more sensors, transducers, and/or othermonitoring elements configured to obtain this diagnostic information. Inthat regard, the one or more sensors, transducers, and/or othermonitoring elements are positioned adjacent a distal portion of theinstrument 132 in some instances. In that regard, the one or moresensors, transducers, and/or other monitoring elements are positionedless than 30 cm, less than 10 cm, less than 5 cm, less than 3 cm, lessthan 2 cm, and/or less than 1 cm from a distal tip 136 of the instrument132 in some instances. In some instances, at least one of the one ormore sensors, transducers, and/or other monitoring elements ispositioned at the distal tip of the instrument 132.

Similar to instrument 130, instrument 132 also includes at least oneelement configured to monitor pressure within the vessel 100. Thepressure monitoring element can take the form a piezo-resistive pressuresensor, a piezo-electric pressure sensor, a capacitive pressure sensor,an electromagnetic pressure sensor, a fluid column (the fluid columnbeing in communication with a fluid column sensor that is separate fromthe instrument and/or positioned at a portion of the instrument proximalof the fluid column), an optical pressure sensor, and/or combinationsthereof. In some instances, one or more features of the pressuremonitoring element are implemented as a solid-state componentmanufactured using semiconductor and/or other suitable manufacturingtechniques. Millar catheters are utilized in some embodiments. Currentlyavailable catheter products suitable for use with one or more ofPhilips's Xper Flex Cardio Physiomonitoring System, GE's Mac-Lab XT andXTi hemodynamic recording systems, Siemens's AXIOM Sensis XP VC11,McKesson's Horizon Cardiology Hemo, and Mennen's Horizon XVu HemodynamicMonitoring System and include pressure monitoring elements can beutilized for instrument 132 in some instances.

In accordance with aspects of the present disclosure, at least one ofthe instruments 130 and 132 is configured to monitor a pressure withinthe vessel 100 distal of the stenosis 108 and at least one of theinstruments 130 and 132 is configured to monitor a pressure within thevessel proximal of the stenosis. In that regard, the instruments 130,132 are sized and shaped to allow positioning of the at least oneelement configured to monitor pressure within the vessel 100 to bepositioned proximal and/or distal of the stenosis 108 as necessary basedon the configuration of the devices. In that regard, FIG. 3 illustratesa position 138 suitable for measuring pressure distal of the stenosis108. In that regard, the position 138 is less than 5 cm, less than 3 cm,less than 2 cm, less than 1 cm, less than 5 mm, and/or less than 2.5 mmfrom the distal end of the stenosis 108 (as shown in FIG. 2 ) in someinstances. FIG. 3 also illustrates a plurality of suitable positions formeasuring pressure proximal of the stenosis 108. In that regard,positions 140, 142, 144, 146, and 148 each represent a position that issuitable for monitoring the pressure proximal of the stenosis in someinstances. In that regard, the positions 140, 142, 144, 146, and 148 arepositioned at varying distances from the proximal end of the stenosis108 ranging from more than 20 cm down to about 5 mm or less. Generally,the proximal pressure measurement will be spaced from the proximal endof the stenosis. Accordingly, in some instances, the proximal pressuremeasurement is taken at a distance equal to or greater than an innerdiameter of the lumen of the vessel from the proximal end of thestenosis. In the context of coronary artery pressure measurements, theproximal pressure measurement is generally taken at a position proximalof the stenosis and distal of the aorta, within a proximal portion ofthe vessel. However, in some particular instances of coronary arterypressure measurements, the proximal pressure measurement is taken from alocation inside the aorta. In other instances, the proximal pressuremeasurement is taken at the root or ostium of the coronary artery.

Referring now to FIG. 4 , shown therein is a system 150 according to anembodiment of the present disclosure. In that regard, FIG. 4 is adiagrammatic, schematic view of the system 150. As shown, the system 150includes an instrument 152. In that regard, in some instances instrument152 is suitable for use as at least one of instruments 130 and 132discussed above. Accordingly, in some instances the instrument 152includes features similar to those discussed above with respect toinstruments 130 and 132 in some instances. In the illustratedembodiment, the instrument 152 is a guide wire having a distal portion154 and a housing 156 positioned adjacent the distal portion. In thatregard, the housing 156 is spaced approximately 3 cm from a distal tipof the instrument 152. The housing 156 is configured to house one ormore sensors, transducers, and/or other monitoring elements configuredto obtain the diagnostic information about the vessel. In theillustrated embodiment, the housing 156 contains at least a pressuresensor configured to monitor a pressure within a lumen in which theinstrument 152 is positioned. A shaft 158 extends proximally from thehousing 156. A torque device 160 is positioned over and coupled to aproximal portion of the shaft 158. A proximal end portion 162 of theinstrument 152 is coupled to a connector 164. A cable 166 extends fromconnector 164 to a connector 168. In some instances, connector 168 isconfigured to be plugged into an interface 170. In that regard,interface 170 is a patient interface module (PIM) in some instances. Insome instances, the cable 166 is replaced with a wireless connection. Inthat regard, it is understood that various communication pathwaysbetween the instrument 152 and the interface 170 may be utilized,including physical connections (including electrical, optical, and/orfluid connections), wireless connections, and/or combinations thereof.

The interface 170 is communicatively coupled to a computing device 172via a connection 174. Computing device 172 is generally representativeof any device suitable for performing the processing and analysistechniques discussed within the present disclosure. In some embodiments,the computing device 172 includes a processor, random access memory, anda storage medium. In that regard, in some particular instances thecomputing device 172 is programmed to execute steps associated with thedata acquisition and analysis described herein. Accordingly, it isunderstood that any steps related to data acquisition, data processing,instrument control, and/or other processing or control aspects of thepresent disclosure may be implemented by the computing device usingcorresponding instructions stored on or in a non-transitory computerreadable medium accessible by the computing device. In some instances,the computing device 172 is a console device. In some particularinstances, the computing device 172 is similar to the s5™ Imaging Systemor the s5i™ Imaging System, each available from Volcano Corporation. Insome instances, the computing device 172 is portable (e.g., handheld, ona rolling cart, etc.). Further, it is understood that in some instancesthe computing device 172 comprises a plurality of computing devices. Inthat regard, it is particularly understood that the different processingand/or control aspects of the present disclosure may be implementedseparately or within predefined groupings using a plurality of computingdevices. Any divisions and/or combinations of the processing and/orcontrol aspects described below across multiple computing devices arewithin the scope of the present disclosure.

Together, connector 164, cable 166, connector 168, interface 170, andconnection 174 facilitate communication between the one or more sensors,transducers, and/or other monitoring elements of the instrument 152 andthe computing device 172. However, this communication pathway isexemplary in nature and should not be considered limiting in any way. Inthat regard, it is understood that any communication pathway between theinstrument 152 and the computing device 172 may be utilized, includingphysical connections (including electrical, optical, and/or fluidconnections), wireless connections, and/or combinations thereof. In thatregard, it is understood that the connection 174 is wireless in someinstances. In some instances, the connection 174 includes acommunication link over a network (e.g., intranet, internet,telecommunications network, and/or other network). In that regard, it isunderstood that the computing device 172 is positioned remote from anoperating area where the instrument 152 is being used in some instances.Having the connection 174 include a connection over a network canfacilitate communication between the instrument 152 and the remotecomputing device 172 regardless of whether the computing device is in anadjacent room, an adjacent building, or in a different state/country.Further, it is understood that the communication pathway between theinstrument 152 and the computing device 172 is a secure connection insome instances. Further still, it is understood that, in some instances,the data communicated over one or more portions of the communicationpathway between the instrument 152 and the computing device 172 isencrypted.

The system 150 also includes an instrument 175. In that regard, in someinstances instrument 175 is suitable for use as at least one ofinstruments 130 and 132 discussed above. Accordingly, in some instancesthe instrument 175 includes features similar to those discussed abovewith respect to instruments 130 and 132 in some instances. In theillustrated embodiment, the instrument 175 is a catheter-type device. Inthat regard, the instrument 175 includes one or more sensors,transducers, and/or other monitoring elements adjacent a distal portionof the instrument configured to obtain the diagnostic information aboutthe vessel. In the illustrated embodiment, the instrument 175 includes apressure sensor configured to monitor a pressure within a lumen in whichthe instrument 175 is positioned. The instrument 175 is in communicationwith an interface 176 via connection 177. In some instances, interface176 is a hemodynamic monitoring system or other control device, such asSiemens AXIOM Sensis, Mennen Horizon XVu, and Philips Xper IMPhysiomonitoring 5. In one particular embodiment, instrument 175 is apressure-sensing catheter that includes fluid column extending along itslength. In such an embodiment, interface 176 includes a hemostasis valvefluidly coupled to the fluid column of the catheter, a manifold fluidlycoupled to the hemostasis valve, and tubing extending between thecomponents as necessary to fluidly couple the components. In thatregard, the fluid column of the catheter is in fluid communication witha pressure sensor via the valve, manifold, and tubing. In someinstances, the pressure sensor is part of interface 176. In otherinstances, the pressure sensor is a separate component positionedbetween the instrument 175 and the interface 176. The interface 176 iscommunicatively coupled to the computing device 172 via a connection178.

Similar to the connections between instrument 152 and the computingdevice 172, interface 176 and connections 177 and 178 facilitatecommunication between the one or more sensors, transducers, and/or othermonitoring elements of the instrument 175 and the computing device 172.However, this communication pathway is exemplary in nature and shouldnot be considered limiting in any way. In that regard, it is understoodthat any communication pathway between the instrument 175 and thecomputing device 172 may be utilized, including physical connections(including electrical, optical, and/or fluid connections), wirelessconnections, and/or combinations thereof. In that regard, it isunderstood that the connection 178 is wireless in some instances. Insome instances, the connection 178 includes a communication link over anetwork (e.g., intranet, internet, telecommunications network, and/orother network). In that regard, it is understood that the computingdevice 172 is positioned remote from an operating area where theinstrument 175 is being used in some instances. Having the connection178 include a connection over a network can facilitate communicationbetween the instrument 175 and the remote computing device 172regardless of whether the computing device is in an adjacent room, anadjacent building, or in a different state/country. Further, it isunderstood that the communication pathway between the instrument 175 andthe computing device 172 is a secure connection in some instances.Further still, it is understood that, in some instances, the datacommunicated over one or more portions of the communication pathwaybetween the instrument 175 and the computing device 172 is encrypted.

It is understood that one or more components of the system 150 are notincluded, are implemented in a different arrangement/order, and/or arereplaced with an alternative device/mechanism in other embodiments ofthe present disclosure. For example, in some instances, the system 150does not include interface 170 and/or interface 176. In such instances,the connector 168 (or other similar connector in communication withinstrument 152 or instrument 175) may plug into a port associated withcomputing device 172. Alternatively, the instruments 152, 175 maycommunicate wirelessly with the computing device 172. Generallyspeaking, the communication pathway between either or both of theinstruments 152, 175 and the computing device 172 may have nointermediate nodes (i.e., a direct connection), one intermediate nodebetween the instrument and the computing device, or a plurality ofintermediate nodes between the instrument and the computing device.

In some embodiments of the present disclose, a ratio of intravascularpressure measurements obtained during a portion of the heartbeat cycleor diagnostic window is calculated. For example, FIG. 5 includesgraphical representation 220 having a plot 222 representative ofpressure (measured in mmHg) within a vessel over the time period of onecardiac cycle and a plot 224 representative of velocity (measured inm/s) of a fluid within the vessel over the same cardiac cycle. FIG. 5 isannotated to identify a diagnostic window 236. The diagnostic windowidentifies a portion of the heartbeat cycle of the patient where theresistance (e.g., pressure divided by velocity) within vasculature isreduced without the use of a hyperemic agent or other stressingtechnique. That is, the diagnostic window 236 corresponds to a portionof the heartbeat cycle of a resting patient that has a naturally reducedand relatively constant resistance.

The portion of the heartbeat cycle coinciding with the diagnostic window236 can be utilized to evaluate a stenosis of the vessel of a patientwithout the use of a hyperemic agent or other stressing of the patient'sheart. In particular, the pressure ratio (e.g., distal pressure dividedby proximal pressure) across the stenosis is calculated for the timeperiod corresponding to the diagnostic window 236 for one or moreheartbeats. The calculated pressure ratio is an average over thediagnostic window in some instances. By comparing the calculatedpressure ratio to a threshold or predetermined value, a physician orother treating medical personnel can determine what, if any, treatmentshould be administered. In that regard, in some instances, a calculatedpressure ratio above a threshold value (e.g., 0.80 on a scale of 0.00 to1.00) is indicative of a first treatment mode (e.g., no treatment, drugtherapy, etc.), while a calculated pressure ratio below the thresholdvalue is indicative of a second, more invasive treatment mode (e.g.,angioplasty, stent, etc.). In some instances, the threshold value is afixed, preset value. In other instances, the threshold value is selectedfor a particular patient and/or a particular stenosis of a patient. Inthat regard, the threshold value for a particular patient may be basedon one or more of empirical data, patient characteristics, patienthistory, physician preference, available treatment options, and/or otherparameters. Various aspects of the diagnostic window, includingidentification of the diagnostic window, features of the diagnosticwindow, etc., are described in U.S. application Ser. No. 13/460,296,titled “Devices, Systems, and Methods for Assessing a Vessel,” and filedApr. 30, 2012, the entirety of which is incorporated by referenceherein.

Referring now to FIGS. 6-8 , shown therein are various graphicalrepresentations of techniques for determining start and/or end pointsfor a diagnostic window in conjunction with an ECG signal in accordancewith the present disclosure. The graphical representation 700 of FIG. 6illustrates a proximal pressure waveform 302, a distal pressure waveform304, and an associated ECG waveform 705. The proximal pressure waveform302 and distal pressure waveform 304 are representative of proximal anddistal pressure measurements obtained within the vasculature. The ECGwaveform 705 is representative of an ECG signal of the patient obtainedat the same time as the proximal and distal pressure measurements areobtained. In that regard, the waveforms 302, 304, 705 in FIGS. 6-8 arearranged to show how the illustrated physiological attributes aregenerally aligned in time.

Referring again to FIG. 6 , a computing device can identify feature(s)of a diagnostic window, pressure waveform(s) 302, 304, and/or thepatient's cardiac cycle based on the ECG waveform 705. For example,using the peak of the R-wave in the ECG waveform 705, the computingdevice can identify a minimum pressure value or valley 701, 703 for eachcardiac cycle. In particular, the peak of the R-wave in the ECG waveform705 occurs at a time 702 that corresponds to the minimum pressure value701 in the distal pressure waveform 304. The next peak of the R-wave inthe ECG waveform 705 (for the next cardiac cycle) occurs at a time 704that corresponds to the minimum pressure value 703 in the distalpressure waveform 304. In that regard, the minimum pressure value 701corresponds to a cardiac cycle (n), and the minimum pressure value 703corresponds to a next cardiac cycle (n+1). The time 702 corresponds tothe beginning of the cardiac cycle (n) and/or the beginning of systole(n). The time 704 corresponds to the end of the cardiac cycle (n),beginning of the next cardiac cycle (n+1), the end of diastole (n),and/or the beginning of systole (n+1). While the distal pressurewaveform 304 is specifically mentioned in this discussion, it isunderstood that the proximal pressure waveform 302 can be similarlyutilized. Generally, at least one identifiable feature of the ECG signal(including without limitation, the start of a P-wave, the peak of aP-wave, the end of a P-wave, a PR interval, a PR segment, the beginningof a QRS complex, the start of an R-wave, the peak of an R-wave, the endof an R-wave, the end of a QRS complex (J-point), an ST segment, thestart of a T-wave, the peak of a T-wave, and the end of a T-wave) canutilized to select that starting point and/or ending point of thediagnostic window, identify features of the proximal or distal pressurewaveforms 302, 304, etc., as described for example, in U.S. applicationSer. No. 13/460,296, titled “Devices, Systems, and Methods for Assessinga Vessel,” and filed Apr. 30, 2012, the entirety of which isincorporated by reference herein.

Referring now to FIG. 7 , shown therein is a graphical representation711 of selecting a diagnostic window based on the feature(s) of thepressure waveform(s) identified using the ECG signal. In some instances,the starting point 710 and/or ending point 714 of the diagnostic window716 is determined by adding or subtracting a fixed amount of time 708,712 to an identifiable feature of the ECG signal. In that regard, thefixed amount time 708, 712 can be a percentage of the cardiac cycle 706in some instances. In that regard, the diagnostic window or wave-freeperiod 716 can be identified based on the minimum pressure values 701,703. For example, the time period 706 between the minimum pressurevalues 701, 703 corresponds to the duration of a cardiac cycle. Acomputing device can select a beginning point 710 of the diagnosticwindow 716 to be positioned a fixed percentage of the total cardiaccycle time 706 from the time 702. That is, the beginning point 710 ofthe diagnostic window can be offset by a period 708 from the time 702 ofthe minimum pressure value 701. A computing device can select an endingpoint 714 of the diagnostic window 716 to be positioned a fixedpercentage of the total cardiac cycle time 706 from the time 704. Thatis, the ending point 714 of the diagnostic window can be offset by aperiod 712 from the time 704 of the next minimum pressure value 703.One, the other, or both of the periods 708, 712 can be described as apercentage of the total cardiac cycle time 706, including values betweenabout 5% and about 95%, between about 10% and about 50%, between about20% and 40%, such as 15%, 20%, 25%, 30%, 35%, 40%, and/or other suitablevalues both larger and smaller.

Referring now to FIG. 8 , shown therein is a graphical representation721 of selecting a diagnostic window based on the feature(s) of thepressure waveform(s) identified using the ECG signal, according toanother embodiment of the present disclosure. In that regard, thediagnostic window or wave-free period 732 can be identified based on theminimum pressure values 701, 703. Starting from the minimum pressurevalue 701, a computing device can identify a peak pressure value 720 inthe distal pressure waveform 304. The computing device can identify amaximum negative/down slope value 722 that occurs after the peakpressure value 720. The maximum negative/down slope value 722 identifieswhen the pressure waveform 304 decreases at the fastest rate. Thediagnostic window 732 can be selected within the period 734 between themaximum down slope value 722 and the next minimum pressure value 703. Inthat regard, the computing device can select a beginning point 726 ofthe diagnostic window 732 to be positioned a fixed percentage of theperiod 734 from the time 723. That is, the beginning point 726 of thediagnostic window can be offset by a period 724 from the time 723 of themaximum down slope value 722. A computing device can select an endingpoint 730 of the diagnostic window 732 to be positioned a fixedpercentage of the period 734 from the time 704. That is, the endingpoint 730 of the diagnostic window can be offset by a period 728 fromthe time 704 of the next minimum pressure value 703. One, the other, orboth of the periods 724, 728 can be described as a percentage of theperiod 734, including values between about 10% and about 90%, betweenabout 12% and about 40%, between about 15% and 30%, such as 15%, 20%,25%, and/or other suitable values both larger and smaller. For example,the period 724 can be 25% of the period 734, and the period 728 can be15% of the period 734.

Referring now to FIGS. 9-14 , shown therein are various graphicalrepresentations of techniques for determining start and/or end pointsfor a diagnostic window. In particular, the algorithm described in theFIGS. 9-14 uses a segment-by-segment analysis of the pressurewaveform(s) to identify feature(s) of the cardiac cycle (e.g., thebeginning/ending of a cardiac cycle) and/or the pressure waveform(s)themselves (e.g., a minimum pressure value, a peak pressure value,etc.). The diagnostic window is then selected based on the identifiedfeature(s). In that regard, an ECG signal is not used to identify thediagnostic window, a feature of the pressure waveform(s), and/or afeature of the cardiac cycle. Thus, any discomfort experienced by thepatient associated with obtaining the ECG signal can be advantageouslyavoided.

Referring now to FIG. 9 , shown therein is a graphical representation731 of a distal pressure waveform 705. As described herein, the waveform705 is a based on distal pressure measurements obtained by anintravascular device disposed within vasculature. While a distalpressure waveform is specifically referenced in this discussion, it isunderstood that a proximal pressure waveform can be similarly utilized.Additionally, while the waveforms in FIG. 9 and elsewhere are shown assmooth, it is understood that the waveforms comprise discrete pressuremeasurement(s).

A segment 740 a of the pressure waveform 705 is indicated in FIG. 9 .The segment 740 a identifies a portion of the pressure waveform 705, asubset of the pressure measurements associated with the pressurewaveform 705, and/or a time period associated with the pressure waveform705. As described herein, a period-by-period or segment-by-segmentanalysis is used to identify features of the cardiac cycle and/or thepressure waveform itself. In some instances, time period, period, and/orsegment may be used interchangeably in the discussion herein. The timeperiod or segment 740 a has a segment width (SW). That is, the pressuremeasurements associated with the segment 740 a are obtained over thegiven time. For example, the width or duration of the segment 740 a canbe less than a cardiac cycle duration, encompassing only a portion ofthe cardiac cycle. In various embodiments, the duration of the segment740 a compared to the cardiac cycle duration is between approximately10% and approximately 90%, approximately 10% and approximately 50%,approximately 10% and approximately 40%, including values such as 20%,25%, 30%, 33%, 35%, and/or other suitable values both larger andsmaller. In some instances, a cardiac cycle duration can beapproximately 1 second. For example, the duration of the segment 740 acan be between approximately 0.1 seconds and approximately 0.9 seconds,approximately 0.1 seconds and approximately 0.5 seconds, approximately0.1 seconds and approximately 0.4 seconds, including values such as 0.2seconds, 0.25 seconds, 0.3 seconds, 0.33 seconds, 0.35 seconds, and/orother suitable values both larger and smaller. In some embodiments, thewidth or duration of the segment 740 a varies for each cardiac cycle.For example, time periods associated with different cardiac cycles havedifferent durations. In that regard, the duration of the segment 740 acan be adjusted manually by a user or automatically by a computingdevice. For example, the duration of the segment 740 a can be based onthe cardiac cycle duration of the cardiac cycle. In that regard, thecardiac cycle duration can be described as the duration betweenconsecutive peak pressure values, consecutive minimum pressure values,etc. For example, the duration of the segment 740 a of a cardiac cycle(n) can be based on the duration of one or more earlier cardiac cycles(n−1, n−2, etc.) such that the duration is adaptive to a patient's heartrhythm. In some embodiments, a duration of the time periods is based ona duration of time periods in one or more previous cardiac cycles. Forexample, the duration of the segment 740 a can an average of earliersegment durations. That is, the duration of segment 740 a can be theaverage of multiple, prior segment durations. The number of priorsegments considered can be variable, adjustable manually by a user,and/or adjustable automatically be a computing device. In someembodiments, the width or duration of the segment 740 a can be definedby a quantity of pressure measurements obtained during the segment. Insome embodiments, the duration of the segment 740 a is bounded by amaximum duration and a minimum duration. In some embodiments, theduration of the segment 740 a (e.g., relative to a cardiac cycle) isoptimized during manufacture of an intravascular system, while in otherembodiments, the duration of the segment can be adjusted prior to,during, and/or after an intravascular procedure.

Referring now to FIG. 10 , shown therein is a graphical representation751 illustrating a period-by-period analysis of the pressure waveform705. Also shown is a segment slope waveform 707 illustrating a slope ofthe pressure waveform 705 associated with each segment. According to anaspect of the present disclosure, a period-by-period analysis of theslope of the pressure waveform 705 is used to identify feature(s) of thecardiac cycle (e.g., the beginning/ending of a cardiac cycle) and/or thepressure waveform(s) itself (e.g., a minimum pressure value, a peakpressure value, etc.). Generally, specific patterns exist withinarterial blood pressure waveforms. The patterns, such as maxima (peaks)and minima (valleys) of the pressure waveforms, can be used to identifythe cardiac cycle and the wave-free diagnostic period within the cardiaccycle. In the case of healthy vasculature with a regular cardiac cycle,there are minimal artifacts in the pressure signals. Thus, the peaks andvalleys of the pressure waveforms can be detected by simply finding theminimum and the maximum values, without the aid of massive filteringprocesses. However, the pressure signals from diseased hearts aretypically distorted by abnormal heart operations (e.g., arrhythmia,premature ventricular contraction, etc.) and/or motion artifactsresulting from pressure measurement (e.g., pullback of thepressure-sensing intravascular device). Therefore, complicated filteringprocedures are typically needed to remove those corruptions and to haveclean pressure signals from which to visualize peaks and valleysclearly. In that regard, the algorithm described herein advantageouslyprovides for robust identification of features of the cardiac cycleand/or pressure waveform, even in diseased vasculature and without theneed for extensive signal filtering hardware or software.

FIG. 10 illustrates a plurality of period segments 740 a, 740 b, 740 c.It is understood the segments 740 a-740 c are only a portion of thetotal number of segments used to analyze pressure waveform 705. In someembodiments, the width or duration of each segment 740 a-740 c is thesame for a given cardiac cycle. For example, time periods associatedwith a single cardiac cycle have the same duration. In some embodiments,the each of the segments 740 a-740 c are consecutive or adjacent intime. For example, a beginning point, midpoint, and/or ending point ofthe segments 740 a, 740 b, 740 c can be adjacent in time. For example,every subsequent pressure sample may define the beginning of a differentsegment. Each of the segments 740 a-740 c can be defined by a startingtime, ending time, and/or midpoint time. Consecutive segments can beseparated by a period between about 0.001 seconds and about 0.5 seconds,about 0.001 seconds and 0.1 seconds, and/other suitable values bothlarger and smaller, including the time between consecutive pressuremeasurements. In some embodiments, a starting point of consecutive timeperiods or segments can be offset based on an acquisition rate of anintravascular pressure-sensing device. For example, data can be acquiredfrom the pressure-sensing instrument for 1 ms every 5 ms and/or othersuitable rates. Consecutive time periods can be offset by about 5 ms insuch embodiments and/or other suitable times in different embodiments.In some embodiments, the segments 740 a-740 c are overlapping in time.In that regard, the segments 740 a-740 c can overlap by any suitableamount of time. In some embodiments, the time period associated with theoverlap can be adjusted manually by a user or automatically by acomputing device. In some embodiments, the overlap can be defined by aquantity of pressure measurements. It is understood that the overlapbetween segments 740 a-740 c illustrated in FIG. 10 is exemplary, andother overlap times, both larger and smaller, are contemplated.

The segment slope waveform 707 is a plot of the slope of each timeperiod or segment (such as segments 740 a-740 c) of the pressurewaveform 705. In some embodiments, a computing device can calculate theslope of the pressure waveform 705 calculated at each pressure sample.The slope may be an average slope of the segment, an instantaneous slopeof the segment (e.g., at the beginning point, a midpoint, and/or theending point), and/or other suitable quantity. For the example, theslope may be calculated as a change/difference in two pressuremeasurements divided by the change/difference in time between the twopressure measurements. In that regard, with a sufficiently wide segmentwidth and with an average slope calculated across the entire duration ofthe segment, the slope is advantageously less sensitive to the distortedhigh and low frequency peaks resulting from abnormal vasculatureconditions or motion artifacts from pressure measurements. In someembodiments, the sample location where the average slope is calculatedis at or near the sample in the middle of the segment. For example, theaverage slope, at the midpoint of the segment, may be calculated as thechange/difference in the pressure measurement between the starting pointand the ending point of the segment divided by the change/difference intime between the starting and ending points. As illustrated in FIG. 10 ,the value of the segment slope waveform 707 changes along the pressurewaveform 705 as, e.g., the average slope of each segment of the pressurewaveform 705 is determined. In some instances, the sign or polarity ofthe segment slope waveform 707 switches between positive and negative(or vice versa).

The slope of multiple time periods or segments 745 a, 745 b, 745 c, 745d, 745 e, 745 f is also illustrated in FIG. 10 . In that regard, each ofthe segments 745 a-745 f is represented by a linear segment spanning itsassociated pressure measurements on the pressure waveform 705. That is,the length of the linear segments can correspond to the duration orwidth of the segments 745 a-745 f. As described with respect to segments740 a-740 c, for a given cardiac cycle, the segments 745 a-745 f haveequal width or span the same amount of time. The linear segments arealso shown as angled to match the average slope associated with thesegments 745 a-745 f. For example, the segment 745 a spans a portion ofthe pressure waveform 705 having a generally positive slope.Correspondingly, the linear segment for segment 745 a is shown having agenerally positive slope. Segments 745 b-745 f variously span differentportions the pressure waveform 705 that having positive slope, zeroslope, and/or negative slope. As the influence of the zero slope ornegative slope portions increases (towards the right of pressurewaveform 705), the linear segments are illustrated as having lesspositive slope than segment 745 a. For example, segments 745 b, 745 cspan portions of the pressure waveform 705 having zero slope andnegative slope. Thus, the linear segment associated with segments 745 b,745 c have a less positive slope, compared to the linear segmentassociated with segment 745 a, which only spans portions of the pressurewaveform 705 having positive slope. Segment 745 d spans portions of thepressure waveform 705 with an average slope of zero. Thus, the linearsegment is illustrated as having zero slope. Segments 745 e and 745 fspan relatively larger portions of the pressure waveform 705 withnegative slope, and, thus, the corresponding linear segments havenegative slopes. The corresponding slope values are plotted in thesegment slope waveform 707. Generally, the slope of the segments 745a-745 f changes in the direction indicated by arrow 713. The portion ofthe pressure waveform 705 spanned by the segments 745 a-745 f includes achange in slope sign. This is illustrated by the linear segments forsegments 745 a-745 f changing slope from positive to negative. Likewise,the segment slope waveform 707 corresponding to the area of segments 745a-745 f starts positive, crosses the zero line, and becomes negative.

Referring now to FIG. 11 , shown therein is a graphical representation751 including the pressure waveform 705 and segment slope waveform 707,similar to that of graphical representation 741 (FIG. 10 ). Graphicalrepresentation 751 also includes a segment slope waveform 709 that isoffset from the segment slope waveform 707 by a period 742. In thatregard, the period 742 can correspond to a calculation delay inembodiments in which the segment slope is calculated around the pressuresample at or near middle of the segment 740 a. Thus, in suchembodiments, the first segment slope is calculated only afterapproximately half of the duration of the segment 740 a. In general, theperiod 742 can be described as a multiple of the segment width (a*SW).In that regard, the multiple can be greater than, equal to, or less thanone (a>1, a=1, or a<1) in different embodiments. For example, themultiple (a) can be between about 0.01 and about 0.99, about 0.1 andabout 0.9, about 0.3 and about 0.7, including values such as 0.35, 0.4,0.45, 0.5, 0.55, 0.6, 0.65, and/or other suitable values both larger andsmaller. FIG. 11 illustrates that values of the segment slope waveform707 can be shifted to account for the calculation delay. For example,the slope 744 a is shifted in the direction 743 by a time equaling theperiod 742, which yields the slope 744 b. The shifted segment slopewaveform 709 results when all values for the segment slope waveform 707are similarly modified. In some embodiments, the algorithm describedherein that identifies features of the diagnostic window, cardiac cycle,and/or the pressure waveform utilizes the shifted waveform 709.

Referring now to FIG. 12 , shown therein a graphical representation 761including the pressure waveform 705 and the segment slope waveform 709.Also illustrated is a feature plot 711, identifying when minima (valley)and maxima (peak) of the pressure waveform 705 occur. In that regard,the waveforms 705, 709, 711 in FIG. 12 and elsewhere are arranged showalignment in time or the simultaneous occurrence of one or morephysiological attributes. According to aspects of the presentdisclosure, the minima 762, 766 and maxima 764, 768 of the pressurewaveform 705 are identified based on when the sign changes in segmentslope waveform 709. The minima 762 (n−1) of the pressure waveform 705can correspond to the beginning of the cardiac cycle (n−1) and/or thebeginning of systole (n−1). The next minima 766 (n) can correspond tothe end of the cardiac cycle (n−1), the end of diastole (n−1), thebeginning of the cardiac cycle (n), and/or the beginning of systole (n).Thus, the features of the cardiac cycle can also be identified based onwhen sign changes in segment slope waveform 709. Correspondingly, thediagnostic window (e.g., the beginning, the ending, etc.) can beselected based on when the sign changes in segment slope waveform 709.

The sign of the segment slope waveform 709 changes at times 747, 749,753, 755. In particular, the sign of the segment slope waveform 709changes from positive to negative at times 747 and 753. The locations746, 750 in segment slope waveform 709 correspond to these positive tonegative sign changes. The minima 762, 766 of the pressure waveform 705can be identified based on the location the sign of the segment slopewaveform 709 changes from positive to negative. For example, the minimum762 can occur at a time 763, prior to the time 747 associated with thesign change 746. In an embodiment, the time 763 occurs at half of thesegment width before the time 747. Thus, the minimum 762 is offset fromthe sign change 746. Generally, the period 754 separating thepositive-to-negative sign change and the minimum pressure measurementcan be a multiple of the segment width (b*SW). In that regard, themultiple can be greater than, equal to, or less than one (b>1, b=1,orb<1) in different embodiments. For example, the multiple (c) can bebetween about 0.01 and about 2, about 0.1 and about 0.9, about 0.3 andabout 0.7, including values such as 0.35, 0.4, 0.45, 0.5, 0.55, 0.6,0.65, and/or other suitable values both larger and smaller. Similarly,the minimum 766 can occur at a time 767, prior to the time 753associated with the sign change 750. Thus, the minimum 766 is offsetfrom the sign change 750. The period 758 separating the times 753, 767can be a multiple of the segment width. In that regard, because theminima 762, 766 are associated with different heart beat cycles, theperiods 754, 758 can be different in some instances.

The value of the segment slope waveform 709 changes from negative topositive at times 749 and 755. The locations 748, 752 in segment slopewaveform 709 correspond to these negative-to-positive sign changes. Themaxima 764, 768 of the pressure waveform 705 can be identified based onthe location the sign of the segment slope waveform 709 changes fromnegative to positive. For example, the maximum 764 can occur at a time765, prior to the time 749 associated with the sign change 748. In anembodiment, the time 765 occurs at 125% of the segment width before thetime 749. Thus, the maximum 764 can be offset from the sign change 748.Generally, the period 756 separating the negative-to-positive signchange and the peak pressure measurement can be a multiple of thesegment width (c*SW). In that regard, the multiple can be greater than,equal to, or less than one (c>1, c=1, or c<1) in different embodiments.For example, the multiple (c) can be between about 0.1 and about 2,about 1 and about 2, about 1.1 and about 1.5, including values such as1.1, 1.2, 1.25, 1.3, 1.35, 1.4, and/or other suitable values both largerand smaller. Similarly, the maximum 768 can occur at a time 775, priorto the time 755 associated with the sign change 752. Thus, the maximum768 can be offset from the sign change 752. The period 760 separatingthe times 755, 775 is a multiple of the segment width. In the regard,because the maxima 764, 768 are associated with different heart beatcycles, the periods 756, 760 can be different in some instances.

The feature plot 711 illustrates the location of the minima (valley) andmaxima (peak) of the pressure waveform 705. In that regard, the valley(n−1) 770, associated with a cardiac cycle (n−1), is aligned with thetime 763 that occurs a period 754 before the positive-to-negative signchange 746. The valley (n) 774, associated with the next cardiac cycle(n), is aligned with the time 767 that occurs a period 758 before thepositive-to-negative sign change 750. The peak (n−1) 764, associatedwith a cardiac cycle (n−1), is aligned with the time 765 that occurs aperiod 756 before the negative-to-positive sign change 748. The peak (n)768, associated with the next cardiac cycle (n), is aligned with thetime 775 that occurs a period 760 before the negative-to-positive signchange 752.

Referring now to FIG. 13 , shown therein is a graphical representation771 of selecting the diagnostic window 792. The starting point 794and/or the ending point 796 of the diagnostic window 792 can be selectedbased on the sign change(s) of the slope. For example, the diagnosticwindow can be selected using the identified minima 762, 766 and maxima764, 768 based on the sign change(s) in the slope of the pressurewaveform. In some embodiments, the starting point 794 of the diagnosticwindow 792 can be offset from the peak pressure measurement, and theending point 796 can be offset from the minimum pressure measurements.In some embodiments, the starting point 794 and/or the ending point 796can selected based on different slope sign changes. For example, thestarting point 794 can be selected based on a negative-to-positive slopesign change, and the ending point 796 can be selected based on apositive-to-negative slope sign change. In some embodiments, thestarting point 794 can be offset from the negative-to-positive signchange, and the ending point 796 can be offset from thepositive-to-negative sign change.

In some embodiments, a computing device can identify the maximumnegative/down slope 780 that occurs after the maximum or peak pressurevalue 764. The diagnostic window 792 can be selected within the period789 between the maximum negative/down slope value 780 and the nextminimum pressure value 766. In that regard, the computing device canselect a beginning point 794 of the diagnostic window 792 to bepositioned a fixed percentage of the period 789 from the time 784. Thatis, the beginning point 794 of the diagnostic window can be offset by aperiod 788 from the time 784 of the maximum negative/down slope value780. A computing device can select an ending point 796 of the diagnosticwindow 792 to be positioned a fixed percentage of the period 789 fromthe time 786. That is, the ending point 796 of the diagnostic window canbe offset by a period 790 from the time 786 of the next minimum pressurevalue 766. One, the other, or both of the periods 788, 790 can bedescribed as a percentage of the period 789, including values betweenabout 10% and about 90%, between about 12% and about 40%, between about15% and 30%, as 15%, 20%, 25%, and/or other suitable values both largerand smaller. For example, the period 788 can be 25% of the period 789,and the period 790 can be 15% of the period 789.

Referring now to FIG. 14 , shown therein is flow diagram of a method 800of evaluating a vessel of a patient. As illustrated, the method 800includes a number of enumerated steps, but implementations of the method800 may include additional steps before, after, and in between theenumerated steps. In some implementations, one or more of the enumeratedsteps may be omitted or performed in a different order. One or more ofthe steps of the method 800 may be performed by processing unit orprocessor, such as the computing device 172 (FIG. 4 ). One or more ofthe steps of the method 800 can be carried out by a user, such as acardiologist or other medical professional.

At step 805, the method 800 includes introducing a first intravascularpressure-sensing instrument into a vessel of a patient proximal of astenosis of vessel. In some embodiments, a catheter, guide wire, or aguide catheter with a pressure sensor can be inserted into, e.g., acoronary artery such that at least a portion of the instrument (e.g.,the portion including the pressure sensor) is positioned proximal of astenosis of the vessel. At step 810, the method 800 includes introducinga second intravascular pressure-sensing instrument into the vesseldistal of the stenosis of the vessel. In some embodiments, a catheter,guide wire, or a guide catheter with a pressure sensor can be insertedinto, e.g., a coronary artery such that at least a portion of theinstrument (e.g., the portion including the pressure sensor) ispositioned distal of the stenosis of the vessel. In some embodiments,the intravascular pressure-sensing instrument positioned proximally ofthe stenosis is a catheter or guide catheter, and the intravascularpressure-sensing instrument positioned distally of the stenosis is aguide wire.

At step 815, the method 800 includes receiving, at a computing device ofan intravascular processing system, proximal and distal pressuremeasurements respectively obtained by first and second intravascularpressure-sensing instruments. The computing device is in communicationwith first and second intravascular pressure-sensing instruments. Theproximal and distal pressure measurements can be obtained during one ormore cardiac cycles of the patient. The proximal and distal pressuremeasurements can be obtained without administration of a hyperemic agentto the patient.

At step 820, the method 800 includes selecting, by the computing deviceof the intravascular processing system, a diagnostic window within thecardiac cycle of the patient. The diagnostic window encompasses only aportion of the cardiac cycle of the patient. In some embodiments, theselecting a diagnostic window does not include using electrocardiogram(ECG) data to, e.g., identify a beginning of a cardiac cycle. Thediagnostic window can be selected by identifying a change in sign of aslope associated with at least one of the proximal pressure measurementsor the distal pressure measurements. In that regard, the method 800 caninclude calculating the slope over multiple time periods. In someembodiments, a single time period encompasses only a portion of thecardiac cycle. In some embodiments, time periods associated with asingle cardiac cycle have the same duration. In some embodiments, acomputing device or processing unit calculates the slope over timeperiods of multiple cardiac cycles. The time periods associated with afirst cardiac cycles can have different duration than the time periodsassociated with the second cardiac cycle. In some embodiments, aduration of the time periods is based on a duration of time periods inone or more previous cardiac cycles. In some embodiments, a duration ofa time period is based on an average of earlier time period durations.In some embodiments, consecutive time periods at least partially overlapin time. In some embodiments, a starting point of consecutive timeperiods are offset based on an acquisition rate of the at least onepressure-sensing instrument.

The method 800 can include identifying a sign change of the slope basedon the slope calculated over the plurality of time periods. That is,slopes respectively associated with the plurality of segments can changepolarity or sign from positive to negative or from negative to positive.The method 800 can include determining, based on the sign change of theslope, a minimum pressure measurement, a peak pressure measurement, abeginning of the cardiac cycle, an ending of the cardiac cycle, abeginning of systole, an ending of diastole, a starting point of thediagnostic window, and/or an ending point of the diagnostic window.

In some embodiments, the diagnostic window can be selected based on thetime during the cardiac cycle at which the sign of the slopes changes. Acomputing device or processing unit can determine a starting point ofthe diagnostic window based on the sign change of the slope. Thestarting point of the diagnostic window can be offset from the signchange of the slope. In some embodiments, a peak pressure measurementcan be determined based on the sign change of the slope. The peakpressure measurement can be offset from the sign change of the slope. Acomputing device or processing unit can determine a starting point ofthe diagnostic window based on the peak pressure measurement. Thestarting point of the diagnostic window can be offset from the peakpressure measurement. In some embodiments, the method 800 furtherdetermining a maximum negative slope occurring after the peak pressuremeasurement. For example, the maximum negative slope point can occurbetween an identified peak pressure measurement (cardiac cycle n−1) anda next identified minimum pressure measurement (cardiac cycle n). Acomputing device or processing unit can determine a starting point ofthe diagnostic window based on the maximum negative slope. The startingpoint of the diagnostic window can be offset from the maximum negativeslope.

In some embodiments, the method 800 further includes determining asecond or further sign change of the slope. A computing device orprocessing unit can determine a minimum pressure measurement based onthe further sign change of the slope. The minimum pressure measurementcan be offset from the further sign change of the slope. A computingdevice or processing unit can determine an ending point of thediagnostic window based on the minimum pressure measurement. The endingpoint of the diagnostic window can be offset from the minimum pressuremeasurement.

At step 825, the method 800 includes identifying, by the computingdevice of the intravascular processing system, a plurality of the distalpressure measurements obtained during the diagnostic window from thereceived distal pressure measurements. The plurality of distal pressuremeasurements are selected based on the selected diagnostic window andare a subset of the received distal pressure measurements. Step 825similarly includes identifying, by the computing device of theintravascular processing system, a plurality of the proximal pressuremeasurements obtained during the diagnostic window from the receivedproximal pressure measurements. The plurality of proximal pressuremeasurements are selected based on the selected diagnostic window andare a subset of the received proximal pressure measurements. An exampleof identifying a plurality of the pressure measurements obtained duringthe diagnostic window is described in U.S. application Ser. No.13/460,296, titled “Devices, Systems, and Methods for Assessing aVessel,” and filed Apr. 30, 2012, the entirety of which is incorporatedby reference herein.

At step 830, the method 800 includes calculating, by computing device, apressure ratio between an average of the plurality of distal pressuremeasurements obtained during the diagnostic window and an average of theplurality of proximal pressure measurements obtained during thediagnostic window. An example of calculating the pressure ratio isdescribed in U.S. application Ser. No. 13/460,296, titled “Devices,Systems, and Methods for Assessing a Vessel,” and filed Apr. 30, 2012,the entirety of which is incorporated by reference herein.

At step 835, the method 800 includes outputting the calculated pressureratio to display device in communication with computing device. In someembodiments, the proximal and distal pressure measurements are aligned(with respect to time) before the pressure ratio is calculated, asdescribed, for example, in U.S. application Ser. No. 14/157,404, titled“Devices, Systems, and Methods for Assessing a Vessel,” and filed Jan.16, 2014; and/or U.S. application Ser. No. 13/460,296, titled “Devices,Systems, and Methods for Assessing a Vessel,” and filed Apr. 30, 2012,the entireties of which is incorporated by reference herein. Forexample, alignment can be performed when the user selects anormalization option provided by the intravascular system. Once thenormalization is ordered, the amount of misalignment is calculated bycross-correlating the proximal and distal pressure measurements pressurefor every heart cycle until the fifth cycle. To complete thenormalization, the pressure measurements, for each heart cycle, can beshifted by an average of the five cycles.

At step 840, the method 800 includes identifying a treatment optionbased on the calculated pressure ratio. For example, the treatmentoption can be no treatment, drug therapy, a percutaneous coronaryintervention (PCI), such as angioplasty and/or stenting, a coronaryartery bypass grafting (CABG) procedure, and/or other suitable clinicalinterventions including combinations of the foregoing options. At step845, the method 800 includes performing the identified treatment option.

Persons skilled in the art will also recognize that the apparatus,systems, and methods described above can be modified in various ways.Accordingly, persons of ordinary skill in the art will appreciate thatthe embodiments encompassed by the present disclosure are not limited tothe particular exemplary embodiments described above. In that regard,although illustrative embodiments have been shown and described, a widerange of modification, change, and substitution is contemplated in theforegoing disclosure. It is understood that such variations may be madeto the foregoing without departing from the scope of the presentdisclosure. Accordingly, it is appropriate that the appended claims beconstrued broadly and in a manner consistent with the presentdisclosure.

What is claimed is:
 1. A system comprising: at least one intravascularpressure-sensing instrument comprising at least one of a catheter or aguide wire; and a processor configured for communication with the atleast one pressure-sensing instrument, wherein the processor configuredto: obtain a plurality of pressure measurements for a cardiac cycle of apatient from the intravascular pressure-sensing instrument while theintravascular pressure-sensing instrument is positioned within a vessel;calculate, for the cardiac cycle, a plurality of slopes of the pluralityof pressure measurements, wherein the plurality of slopes isrepresentative of an entirety of the cardiac cycle; identify a change insign of the plurality of slopes, wherein the change in sign comprises:from a first sign to a second sign; or from the second sign to the firstsign; select a subset of the plurality of the pressure measurementsbased on the change in sign; calculate a pressure ratio using the subsetof the plurality of pressure measurements; and output the pressure ratioto a display device in communication with the processor.
 2. The systemof claim 1, wherein the processor is configured to: determine a startingpoint or an ending point of the subset based on the change in sign. 3.The system of claim 2, wherein the processor is configured to: determinea peak pressure measurement of the plurality of pressure measurementsbased on the change in sign; determine a maximum negative slope of theplurality of slopes occurring after the peak pressure measurement; anddetermine the starting point of the subset based on the maximum negativeslope.
 4. The system of claim 3, wherein processor is configured to:calculate each of the plurality of slopes over a same segment duration;determine the peak pressure measurement based on a first multiplier andthe segment duration.
 5. The system of claim 4, wherein the processor isconfigured to determine the starting point of the subset such that thestarting point is offset from the maximum negative slope.
 6. The systemof claim 2, wherein the processor is configured to: determine a minimumpressure measurement within the cardiac cycle based on the change insign; and determine the ending point of the subset such that the endingpoint is offset from the minimum pressure measurement.
 7. The system ofclaim 6, wherein the processor is configured to: calculate each of theplurality of slopes over a same segment duration; determine the minimumpressure measurement based on a second multiplier and the segmentduration.
 8. The system of claim 1, wherein the processor is configuredto: calculate each of the plurality of slopes over a same segmentduration; and shift the plurality of slopes in time based on a thirdmultiplier and the segment duration.
 9. The system of claim 1, whereinthe processor is further configured to: calculate each of the pluralityof slopes over a first segment duration; and calculate a furtherplurality of slopes in a further cardiac cycle, wherein the processor isconfigured to calculate each of the further plurality of slopes over asecond segment duration different from the first segment duration. 10.The system of claim 9, wherein the processor is configured to determinethe second segment duration based on a duration of the cardiac cycle.11. The system of claim 1, wherein the processor is configured tocalculate the plurality of slopes for a plurality of corresponding timeperiods, wherein consecutive time periods at least partially overlap intime.
 12. The system of claim 1, wherein the processor is furtherconfigured to determine, based on the change in sign, at least one of aminimum pressure measurement, a peak pressure measurement, a beginningof the cardiac cycle, an ending of the cardiac cycle, a beginning ofsystole, an ending of diastole, a starting point of the subset, or anending point of the subset.
 13. The system of claim 1, wherein thesubset encompasses only a portion of the cardiac cycle of the patient.